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Published on: June 17, 2015
Methylmercury induces apoptosis in cultured rat dorsal root ganglion neurons
Russell A Wilke1, Christopher P Kolbert, Rod A Rahimi
1Personalized Medicine Center, Marshfield Medical Research Foundation, Marshfield Clinic, Marshfield, WI, USA.
Abstract:
Methylmercury is known to have devastating effects on the mammalian nervous system. In order to characterize the dose dependence of methylmercury-induced neurotoxicity, we first studied neurite outgrowth from rat dorsal root ganglia explants. In this model, methylmercury inhibited neurite outgrowth with a TD(50) of approximately 0.5 microM. We then used this relationship to optimize dosing for subsequent transcriptional profiling analyses in two independent neuronal model systems: dissociated sensory neurons and PC12 cells. As seen in previous studies, the expression of a number of genes associated with oxidative stress was altered following a 6h challenge with 1 microM methylmercury. When PC12 cells were subjected to a longer exposure (24h), a relative increase was noted in the representation of genes associated with cell cycling and apoptosis. To confirm the presence of apoptosis in cultured neurons, we then applied TUNEL staining and bis-benzimide staining techniques to primary cultures of dissociated sensory neurons. After 24h, 1 microM methylmercury increased both DNA end-labeling (P<0.01) and nuclear fragmentation (P<0.02). The latter effect appeared to be dose-dependent.
Insights
Methylmercury exposure harms the mammalian nervous system. This study reveals methylmercury
Area of Science:
- Neuroscience
- Toxicology
- Molecular Biology
Background:
- Methylmercury is a potent neurotoxin.
- Its dose-dependent effects on neuronal function require detailed characterization.
- Understanding molecular mechanisms is crucial for risk assessment.
Purpose of the Study:
- To investigate the dose-dependent neurotoxicity of methylmercury.
- To identify molecular pathways affected by methylmercury exposure in neurons.
- To characterize the relationship between methylmercury concentration and neuronal damage.
Main Methods:
- Neurite outgrowth assays using rat dorsal root ganglia explants.
- Transcriptional profiling of dissociated sensory neurons and PC12 cells.
- TUNEL and bis-benzimide staining to detect apoptosis.
Main Results:
- Methylmercury inhibited neurite outgrowth with a TD(50) of ~0.5 microM.
- Short-term exposure (6h) altered oxidative stress gene expression.
- Longer exposure (24h) induced genes related to cell cycling and apoptosis, confirmed by DNA end-labeling and nuclear fragmentation.
Conclusions:
- Methylmercury exhibits dose-dependent neurotoxic effects.
- Oxidative stress, cell cycling, and apoptosis are key pathways involved.
- These findings provide insights into methylmercury's mechanism of neurotoxicity.
